Pradigastat(Pradigastat) - 药物靶点：DGAT1_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Pradigastat (USAN)、Pradigastat sodium、ANJ-908

+ [6]

靶点

DGAT1

作用方式

抑制剂

作用机制

DGAT1抑制剂(二酰基甘油O-酰基转移酶-1抑制剂)

治疗领域

遗传病与畸形内分泌与代谢疾病其他疾病+ [4]

在研适应症-

非在研适应症

脂蛋白脂肪酶循环抑制剂所致家族性乳糜微粒血症功能性便秘冠心病+ [6]

原研机构

Novartis Pharma AG

在研机构-

非在研机构

Novartis Pharmaceuticals Corp.

Novartis Pharmaceuticals Canada, Inc.

安济药业（上海）有限公司

权益机构

安济药业（上海）有限公司

Novartis AG

最高研发阶段终止临床3期

首次获批日期-

最高研发阶段(中国)终止

特殊审评-

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结构/序列

分子式C25H24F3N3NaO2

InChIKeyOPXPCSVCLNFSKI-BHQIMSFRSA-N

CAS号956136-98-4

关联

14

项与 Pradigastat 相关的临床试验

NCT04620161

/ Completed临床2期

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Proof of Concept Study to Assess the Efficacy, Safety and Tolerability of Pradigastat in Patients With Functional Constipation

The purpose of this study is to evaluate the efficacy, safety, and tolerability of pradigastat 20 and 40 mg as compared to placebo in patients with Functional Constipation.

开始日期2020-09-22

申办/合作机构

Anji Pharmaceuticals, Inc.

[+1]

NL-OMON41457

/ Completed临床3期

An open label, long term, safety and tolerability extension to a randomized, double-blind, placebo controlled study of LCQ908 in subjects with Familial Chylomicronemia Syndrome - LCQ908 extension study

开始日期2013-10-31

申办/合作机构

Novartis AG

NCT01811472

/ Completed临床2期

A Randomized, Multicenter, Double-blind, Placebo-controlled, Parallel-group, 24-week Pilot Study to Assess the Efficacy, Safety and Tolerability of LCQ908 in Patients With Non-alcoholic Fatty Liver Disease

The purpose of this study was to determine whether LCQ908 effectively lowers liver fat, as assessed by MRI and to assess its safety and tolerability profile in subjects with non-alcoholic fatty liver disease (NAFLD).

开始日期2013-06-01

申办/合作机构

Novartis Pharmaceuticals Corp.

100 项与 Pradigastat 相关的临床结果

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100 项与 Pradigastat 相关的转化医学

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100 项与 Pradigastat 相关的专利（医药）

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23

项与 Pradigastat 相关的文献（医药）

2024-08-14·mBio

Physiologic medium renders human iPSC-derived macrophages permissive for M. tuberculosis by rewiring organelle function and metabolism

Article

作者: Gutierrez, Maximiliano G ; Athanasiadi, Natalia ; Bussi, Claudio ; Lai, Rachel ; Gutierrez, Maximiliano G.

ABSTRACT:

In vitro studies are crucial for our understanding of the human macrophage immune functions. However, traditional in vitro culture media poorly reflect the metabolic composition of blood, potentially affecting the outcomes of these studies. Here, we analyzed the impact of a physiological medium on human induced pluripotent stem cell (iPSC)-derived macrophages (iPSDM) function. Macrophages cultured in a human plasma-like medium (HPLM) were more permissive to Mycobacterium tuberculosis (Mtb) replication and showed decreased lipid metabolism with increased metabolic polarization. Functionally, we discovered that HPLM-differentiated macrophages showed different metabolic organelle content and activity. Specifically, HPLM-differentiated macrophages displayed reduced lipid droplet and peroxisome content, increased lysosomal proteolytic activity, and increased mitochondrial activity and dynamics. Inhibiting or inducing lipid droplet formation revealed that lipid droplet content is a key factor influencing macrophage permissiveness to Mtb. These findings underscore the importance of using physiologically relevant media in vitro for accurately studying human macrophage function.

IMPORTANCE:

This work compellingly demonstrates that the choice of culture medium significantly influences M. tuberculosis replication outcomes, thus emphasizing the importance of employing physiologically relevant media for accurate in vitro host-pathogen interaction studies. We anticipate that our work will set a precedent for future research with clinical relevance, particularly in evaluating antibiotic efficacy and resistance in cellulo .

2020-06-01·Digestive diseases and sciences3区 · 医学

Use of Accelerated Induction Strategy of Infliximab for Ulcerative Colitis in Hospitalized Patients at a Tertiary Care Center

3区 · 医学

Article

作者: Berinstein, Jeffrey A ; Hardiman, Karin M ; Govani, Shail M ; Waljee, Akbar K ; Stidham, Ryan W ; Higgins, Peter D R

BACKGROUND:

Infliximab can prevent colectomy in patients hospitalized with acute severe ulcerative colitis (ASUC). In cases of ASUC, fecal losses of infliximab may lead to low drug levels and reduced efficacy.

AIM:

To determine 90-day colectomy risk and postoperative complications in patients receiving single-dose and accelerated induction of infliximab for ASUC.

METHODS:

We conducted a retrospective review of patients hospitalized with ASUC requiring infliximab therapy between 2013 and 2017 at the University of Michigan. Patients were excluded if they had an enteric infection, received an anti-TNF previously, or received cyclosporine during the same admission. The primary outcome was colectomy within 90 days of admission. Patients receiving single-dose induction infliximab were compared to those receiving accelerated rescue induction with two doses of infliximab prior to day 14. Administration of accelerated induction was guided by a protocol, suggesting administering a second dose of infliximab to those with only a partial response in CRP 3 days after the initial dose. Postoperative outcomes including 30-day readmission rates and complications were compared using descriptive statistics.

RESULTS:

From 2013 to 2017, 66 patients with ASUC met our criteria. Thirty-three received accelerated induction (50.0%). The colectomy rate in the accelerated induction group was 30.3% versus 24.2% in the single-dose induction group (p = 0.58). There was no detected difference in postoperative outcomes between the accelerated and single-dose rescue induction.

CONCLUSIONS:

In this retrospective review, 69.7% of those failing to respond to single-dose infliximab were able to avoid colectomy with an accelerated rescue induction strategy without worsening postoperative outcomes. Larger studies of accelerated dosing infliximab are needed.

2020-01-01·Journal of enzyme inhibition and medicinal chemistry2区 · 医学

Synthesis and biological evaluation of novel thienopyrimidine derivatives as diacylglycerol acyltransferase 1 (DGAT-1) inhibitors

2区 · 医学

ArticleOA

作者: Min, Kyung Hoon ; Hong, Dong Jin ; Kim, Jisook ; Ahn, Young Gil ; Suh, Kwee Hyun ; Jung, Seung Hyun ; Jung, Danbee

A novel series of thieno[3,2-d]pyrimidine derivatives were synthesised and their inhibitory effects against diacylglycerol acyltransferase 1 (DGAT-1) were assessed. cis-Isomer 17a showed potent and selective inhibitory activity against DGAT-1 in SF9 cells. In addition, 17a had an acceptable pharmacokinetic profile and accumulated mainly in the small intestine and liver. Oral administration of 17a led to a significant reduction in plasma triacylglycerol level during an oral lipid tolerance test (OLTT) in murine and canine models. Taken together, 17a is a high-quality candidate that deserves further investigation.

12

项与 Pradigastat 相关的新闻（医药）

2024-12-15

·药事纵横

华人科学家再联合创业，融了2.15亿美金B轮的Biotech

▲3月6-7日上海长三角新药创新者峰会扫码免费报名注：本文不构成任何投资意见和建议，以官方/公司公告为准；本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及），不代表平台立场。任何文章转载需得到授权。药融圈获悉：减肥领域新药公司Metsera由Population Health Partners和ARCH Venture Partners创立于2022年，总部在美国纽约。2024年4月份，完成的2.9亿美元融资。连续融资：上个月，2024年11月13日，Metsera完成2.15亿美元新一轮B轮融资。本轮融资由Wellington Management和Venrock Healthcare Capital Partners领投；Fidelity、Janus Henderson Investors、T.Rowe Price Associates和T.Rowe Price Investment Management、Viking Global Investors、Deep Track Capital、RA Capital Management新投资者参与了本轮融资。现有Metsera的投资者包括ARCH Venture Partners、Alpha Wave Ventures、GV、SoftBank Vision Fund 2、Newpath Partners、SymBiosis等同样参与本轮。公司的CSO 和转化医学负责人等则是创业老兵，此前在安济药业：安济药业（Anji Pharma）是一家新兴的全球医药公司，由时任首席执行官Brian Hubbard博士创立。他曾在博德研究所、默克、诺华和千年制药等公司领导药物研发。安济药业的联合创始人还包括：首席医学官Dan Meyers博士，曾设计和领导了40多个临床试验；华人首席科学官Mike Serrano-Wu博士，参与研发了daclatasvir、pradigastat和其他5个已进入临床试验阶段的候选药物分子。2022年10月19日，安济药业和Population Health Partners正式宣布达成战略合作。 ▲ Metsera CEO Clive Meanwell Metsera的核心产品MET-097正在进行1/2期试验，本品是一种新型的、偏向的、每月一次注射的GLP-1 候选分子；MET-233i是一种超长效胰淀素类似物（amylin）；其他还有口服GLP-1 肽类MET-002；MET-034i，一种超长效HALO™脂化GIP RA新药；还包括胰岛淀粉样肽/降钙素双重受体激动剂（DACRA），单分子GGG等等。公司拥有一整套营养刺激激素（NuSH）类似肽库用于候选药物开发。 ▲https://pharma.bcpmdata.com/database/24/detail/441/mb94LZMBlWZ1TLUOcEWj 2024年9月，MET-097的一期临床数据披露：MET-097实现380小时的半衰期，将可用于每月给药方案；1.2mg剂量组下，患者治疗5周后（36天）减重7.5%；最后一次停药后4周减重幅度扩大至8.1%，提示药效保持时间与潜在的超长半衰期相符合。体重管理，合理健康减重 2024年10月，Metsera宣布与 Amneal Pharmaceuticals 建立供应链领域合作关系；据悉这家美国上市公司 Amneal 将成为 Metsera 在包括美国和欧洲在内的发达市场的“首选供应合作伙伴”。Amneal 还将拥有在一些新兴市场商业化 Metsera 产品的权益许可。参考： NMPA/CDE 药融云数据，www.pharnexcloud.com；改名后为摩熵医药数据； FDA/EMA/PMDA；相关公司公开披露； https://www.businesswire.com/news/home/20240924023447/en/Metsera-Reports-Highly-Competitive-Results-from-Ongoing-Trial-of-Novel-Potential-Once-Monthly-Injectable-GLP-1-Receptor-Agonist-MET-097； https://metsera.com； https://endpts.com/the-endpoints-11-2024-winners-big-bets-on-ai-new-frontiers-in-editing-a-neuro-renaissance-and-chinese-chemistry/； https://amneal.com/；等等。本文仅用于向医疗卫生专业人士提供科学信息，不代表平台立场，不作任何用药推荐。

临床1期

2024-11-18

·生物制药小编

新晋减肥Biotech：CSO此前是国内企业创始人

尽管近年来GLP-1减肥药赛道拥挤不断，但是仍然有企业能够脱颖而出，融到资金。近日，新晋减肥药公司Metsera宣布了2.15亿的B轮融资，这距离该公司今年4月份2.9亿美元的A轮融资仅仅过去7个月，Metsera显然有从竞争环境中脱颖而出的潜力。卖点：轻微副作用，不涉及剂量渐增，每月一次从该公司9月发布的I期临床信息来看，Metsera目前进度最快的管线是长效可注射GLP-1受体激动剂MET-097，该管线采用Metsera的HALO脂质平台设计。注射间隔为每个月一次，接受MET-097i治疗的参与者在第36天的体重比基线下降了7.5%。比较值得称道的是该药物的安全性效果。一般而言，已批准的减肥药需要通过滴定的缓慢增加剂量来适应剂量的时期，不然就可能出现胃肠道相关副作用。比如说，例如，司美格鲁肽一般被建议从0.25mg小剂量起始，单次注射逐步增加到1mg。而相比于目前市面上的司美格鲁肽和替尔泊肽，MET-097的临床不需要涉及剂量渐增，而且副作用看上去非常轻微。这一方面简化了患者的给药模式，另外一方面还优化了安全性问题。另外，该公司还有该公司有一个完整的营养刺激激素(NuSH)模拟肽库，该肽库建立在大约2万种NuSH模拟肽的基础上，并通过二十年的经验生物学研究和先进的肽工程开发而成，可从中推出多种药物候选物，目前该公司还有MET-034i，MET-233i等管线。目前推测，技术来源于收购GLP-1研究的领军人物Stephen Bloom的小微公司Zihipp和韩国公司D&D Pharmatech。在这种情况下，吸引多位高端投资者的两轮次融资似乎再正常不过，值得一提的是，如果查看Metsera的技术团队，会惊讶地发现CSO是以前一家中国药企的联合创始人之一。 CSO此前是国内企业创始人如果仔细看Metsera的技术掌舵团队，会发现此前与中国Biotech安济药业（Anji Pharma）的一致之处都是CSO Brian Hubbard，研发负责人（转化医学）的Mike Serrano-Wu。这两位显然都是新药猎人“老兵”。安济药业此前是由CRO公司维亚生物所孵化的，董事长也是维亚生物的创始人毛晨博士。CEO是现在博致生物首席运营官宗宜伟博士。当时具有的管线是收购自Elcelyx Therapeutics的ANJ900（二甲双胍延迟释放新剂型）和授权自诺华的DGAT1抑制剂ANJ908（pradigastat），授权自LipimetiX Development（Capstone Therapeutics子公司）的多肽创新药AEM-28。适应症方面，ANJ900旨在针对那些有着慢性肾病的二型糖尿病患者，ANJ908主要用于便秘，AEM-28用于严重的孤儿高胆固醇血症。值得一提的是，维亚生物孵化的另外一家企业 Dogma Therapeutics的技术骨干也是Brian Hubbard和Mike Serrano-Wu，Dogma开发的主要是PCSK9小分子药物，目前已经授权给了阿斯利康，研发代码为AZD0780。总结总的来说，Metsera的崛起速度非常之快，收购管线抓住了现有药物的弊端，做出了差异化，技术团队选取了新药猎人“老兵”掌舵，可以期待未来该公司的更多信息。参考来源： https://metsera.com/news https://www.sohu.com/a/594125812_120455786 https://www.dogmatherapeutics.com/

并购临床1期

2023-05-16

·BioSpace

Trueline Therapeutics Announces Completion of IND-Enabling Studies for MCL1 Inhibitor TTX-810

- TTX-810 is designed for rapid clearance to circumvent mechanism-based risks of MCL1 inhibition - High potency affords robust anti-tumor effects whilst preserving cardiomyocyte viability - Trueline Therapeutics on track to initiate clinical development of TTX-810 CAMBRIDGE, Mass., & BERLIN--(BUSINESS WIRE)-- Trueline Therapeutics Inc., an oncology-focused subsidiary of Anji Pharmaceuticals, today announced the successful completion of IND-enabling studies with MCL1 inhibitor TTX-810, a highly potent and selective macrocyclic compound to treat patients with solid tumor or hematological cancers. A distinguishing feature of TTX-810 is a rapid clearance pro minimize the potential risks of sustained MCL1 inhibition in non-cancerous tissues. “The completion of IND-enabling studies marks the culmination of over a decade’s work to truly understand the safest and most effective way to approach MCL1 inhibition,” said Ulla Rauh, Ph.D., CEO/CSO of Trueline Therapeutics. “With our rapid-clearance strategy further de-risked, we are excited to progress TTX-810 into cancer patients and finally unlock the therapeutic potential of MCL1 inhibition.” TTX-810 was discovered by a partnership between the Broad Institute of Harvard and MIT and Bayer Pharmaceuticals. The exquisite potency of TTX-810 was achieved by structure-guided design and comprehensive profiling versus over 500 cancer cell lines to define the optimal cellular context for rapid and selective induction of cell death. Following candidate selection, Trueline Therapeutics scientists designed and executed the IND-enabling program in preparation for first-in-human testing. “When we first saw the TTX-810 data package, our key questions were ‘Will it work?’ and ‘Will it be safe?’ given the challenges other therapeutic candidates with more traditional clearance profiles are encountering,” said Michael Serrano-Wu, Ph.D., Chief Scientific Officer of Anji Pharmaceuticals. “This approach benefits from the rapid and irreversible effects of MCL1 inhibition, which we believe offers a therapeutic window not attainable with longer-acting compounds. We customized our IND-enabling program to address these questions, and now it is full steam ahead to demonstrate the clinical advantages of this unique profile.” About Trueline Therapeutics Inc. Trueline Therapeutics is an oncology-focused subsidiary of Anji Pharmaceuticals. In addition to the MCL1 inhibitor TTX-810, TruelineTx is developing a CD3/CD33 bi-specific called TTX-564 which has been shown to be safe in cancer patients and induce strong depletion of immunosuppressive cells called myeloid-derived suppressor cells (MDSCs). A dual HCK/BTK inhibitor, TTX-114 is in preclinical development. For more information visit . About Anji Pharmaceuticals Inc. Anji Pharma is a clinical-stage company dedicated to bringing life-changing therapies to patients across the globe. Anji’s asset-centric business model allows for speed and flexibility in building value, leveraging a clinical and regulatory core that operates with “hub-and-spoke” efficiency. Since its founding in 2018, Anji Pharma has launched clinical trials for two late-stage development programs: ANJ900 for glucose management in T2D and CKD and ANJ908 as a new mechanism for chronic constipation. For more information, visit .

临床申请临床研究

100 项与 Pradigastat 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10664	-	-	DB12866

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
家族性乳糜微粒血症综合征	临床3期	美国	Novartis Pharmaceuticals Corp.	2012-07-01
家族性乳糜微粒血症综合征	临床3期	加拿大	Novartis Pharmaceuticals Corp.	2012-07-01
家族性乳糜微粒血症综合征	临床3期	法国	Novartis Pharmaceuticals Corp.	2012-07-01
家族性乳糜微粒血症综合征	临床3期	德国	Novartis Pharmaceuticals Corp.	2012-07-01
家族性乳糜微粒血症综合征	临床3期	荷兰	Novartis Pharmaceuticals Corp.	2012-07-01
家族性乳糜微粒血症综合征	临床3期	南非	Novartis Pharmaceuticals Corp.	2012-07-01
家族性乳糜微粒血症综合征	临床3期	西班牙	Novartis Pharmaceuticals Corp.	2012-07-01
家族性乳糜微粒血症综合征	临床3期	英国	Novartis Pharmaceuticals Corp.	2012-07-01
功能性便秘	临床2期	美国	安济药业（上海）有限公司	2020-10-19
代谢功能障碍相关的脂肪肝病	临床2期	美国	Novartis Pharmaceuticals Corp.	2013-06-01

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01387958 (Pubmed \| ACS Infect Dis) 人工标引	N/A	丙型肝炎	32	Pradigastat	鏇廠窪願壓網窪窪糧網(鹹製艱獵壓範襯淵糧廠) = Most treatment-emergent adverse events were gastrointestinal; there were no hepatic adverse events. 繭餘鬱鑰鏇艱襯鏇觸鑰 (鑰簾壓蓋繭醖簾襯蓋艱 )	不佳	2017-02-10
				Placebo
NCT01474434 (CTgov)	临床2期	高甘油三酯血症 \| 冠心病	41	Pradigastat (LCQ908) (Part A, Cohort 1: Pradigastat (LCQ908))	選築壓膚衊願蓋鹽衊醖(鏇襯齋願顧壓廠選網鹹) = 艱廠網醖顧鑰襯壓淵製顧壓鹽遞夢膚繭遞築齋 (顧窪艱夢醖鏇淵憲觸夢, 0.24) 更多	-	2016-04-14
				placebo (Part A, Cohort 1: Placebo)	選築壓膚衊願蓋鹽衊醖(鏇襯齋願顧壓廠選網鹹) = 積醖夢鏇醖醖繭醖夢範顧壓鹽遞夢膚繭遞築齋 (顧窪艱夢醖鏇淵憲觸夢, 0.24) 更多
NCT01811472 (CTgov)	临床2期	代谢功能障碍相关的脂肪肝病	52	placebo (Placebo)	餘糧鹹鹽壓築鏇鹽廠繭(構齋醖衊顧選艱醖範襯) = 鹽壓鹹積衊窪鹹窪艱顧淵鑰製壓願鬱範構鹹構 (憲選鹽壓願壓鹹鑰膚顧, 鹽鹽構觸選淵夢餘醖艱 ~ 鬱鹹選醖觸願製淵築築) 更多	-	2016-02-04
				LCQ908 (Pradigastat (LCQ908) 5mg/10mg)	餘糧鹹鹽壓築鏇鹽廠繭(構齋醖衊顧選艱醖範襯) = 獵築顧壓繭廠淵廠蓋遞淵鑰製壓願鬱範構鹹構 (憲選鹽壓願壓鹹鑰膚顧, 繭遞鏇鑰製鏇顧窪製憲 ~ 艱膚積構鏇積繭積壓構) 更多
NCT01594957 (Pubmed \| Clin Pharmacokinet) 人工标引	临床1期	肝损伤	16	Pradigastat	願糧膚廠艱鏇選廠襯選(積獵蓋餘鹽蓋壓窪獵淵) = 築糧淵窪積鏇鏇壓醖糧齋糧遞憲衊艱鏇鏇簾夢 (蓋願憲鑰網壓遞淵廠廠 )	积极	2015-07-01
NCT01514461 (CTgov)	临床3期	家族性乳糜微粒血症综合征	45	Placebo (Placebo)	網選餘醖淵製觸衊構鬱(願獵製繭夢蓋糧廠膚鬱) = 鬱齋鏇網醖鑰願鏇艱鬱壓選鑰顧範選襯鏇簾觸 (蓋築遞顧壓選願廠糧糧, 糧製鑰選壓獵襯鬱選襯 ~ 鑰憲醖獵壓遞製觸遞蓋) 更多	-	2015-06-03
				Placebo+LCQ908 (LCQ908 40 mg)	網選餘醖淵製觸衊構鬱(願獵製繭夢蓋糧廠膚鬱) = 簾範鏇夢齋淵遞選艱顧壓選鑰顧範選襯鏇簾觸 (蓋築遞顧壓選願廠糧糧, 蓋築簾蓋艱築醖鬱蓋獵 ~ 鹹鑰壓餘鹽簾積範夢鹹) 更多